Roxie isn't seen until the end of the season premiere, when Damon comes home to get a drink and Roxie is sitting with a blood bag in one of the arm chairs. After casually asking her how she's doing he informs her about Katherine's return and she's obviously bothered. After all, Katherine was the person who tore her brothers apart the first time around. Damon explains that Stefan is not going to let that happen but Roxie doubts he will be able to keep that promise. Suddenly Katherine appears and greets the youngest Salvatore casually. Roxie becomes furious at the sight of her and tries to knock Katherine out but she is both older and stronger and overpowers Roxie and throws her back in her arm chair. One hundred percent done with Damon and Katherine's instant bickering, Roxie leaves the room.
The next day Roxie seems to be in a better mood and attends the High School Carnival. Damon keeps lurking on the Lockwoods to find out their little secret and when Mason beats Stefan at arm wrestling Roxie also becomes interested. However, both Stefan and Roxie think it's a bad idea to reveal what Mason truly is by compelling a student to pick a fight with Tyler. They watch as the fight goes down and it turns out Damon was right; Mason Lockwood is not human. The night takes another unexpected turn when it turns out Katherine has turned Caroline into a vampire. They spread out to find her and when they do she has killed a man. Damon wants to stake her but Stefan protects Caroline and helps her while Roxie and Damon stay with Bonnie and Elena. Bonnie tries to kill Damon but Elena and Roxie stop her. Roxie goes to bury the body of the man Caroline killed.In Bad Moon Rising Damon, Stefan, Roxie, and Elena meet up with Alaric and asks him about Isobel's research, if she ever mentioned any other kind of supernatural creature than vampires. As soon as he mentions lycanthropes, also known as werewolves, it's clear Roxie has been thinking this for a while. Neither of her brothers have met any werewolf in over a century, but Roxanne tells them about the night she met Brady.
- Elena: "Wait, like, werewolves?"
- Roxie: "I told you so."
- Damon: "Impossible. [...] I've never come across one. If werewolves exist, where the hell are they?"
- Roxie: "I have. ---The night I met Brady, I lived in the woods but I was chased off by wolves, but they weren't exactly wolves. They were larger. Faster. And they hated me. And werewolves hate vampires, right?"
- — The group discusses the likelihood of werewolves existing.
In Memory Lane Roxie joins Jenna's barbecue. She's the only one other than Damon and Mason who is aware of the innuendos they're throwing at each other and constantly rolls her eyes. She is not on board with killing Mason, which fails, and Mason doesn't hold a grudge against her while he tells Damon he had just made an enemy before leaving Damon to worry about the consequences to his actions while Roxie silently judges him.
With Jeremy getting more and more involved and Katherine becoming more dangerous as the times passes, Roxie reluctantly gets assigned to keep an eye on him. However, instead of watching from afar she shamelessly sits down at a table with him and Tyler at the Grill and basically invites herself to Tyler's party. At the party, she hears the boys fighting and comes to rescue Jeremy but the fight breaks when she enters the room. Jeremy says he knows about the Lockwood curse and Tyler, who doesn't yet know Roxie is a vampire, tells her to leave. She stubbornly stays. When he tries to push her out himself, she doesn't move an inch. Jeremy tells them how he knows about the Lockwood curse and him and Tyler discuss the matter which lets Roxie know a little more about werewolves, and also about a special moonstone.
She quickly leaves to report back to her brothers what she's found out but they're nowhere to be found. Instead she meets Caroline and Elena in the woods and find out Liz has taken her brothers. Elena and Roxie go to save them but Roxie gets shot due to being a Salvatore. Caroline exposes herself to her mother to save them. The whole situation makes Roxie forget to tell her brothers about the moonstone. However, she does tell Damon about Tyler not being a werewolf since the curse is triggered by killing someone.A few days later (Plan B) Jeremy comes over to tell Damon about what the found out. At first Damon isn't interested since Roxie already told him half of it, but when Jeremy mentions a moonstone, he eventually lets Jeremy inside.
- Damon: "Jeremy here just told me something very interesting. "
- Roxie: "Oh and what is that?"
- Damon: "Something about a moonstone. You were there. Why didn't you spill?"
- Roxie: "Oh, right. I'm sorry, I was too busy recovering from almost getting killed to tell you."
- — Damon confronts Roxie about not telling him about the moonstone.
The next day Jeremy is the first to notice Elena has been kidnapped. Bonnie locates her with a spell and Damon and Stefan go one a road trip to get her back. Roxie joins them to keep them from bickering too much. They work together and manage to save her from Original Vampire Elijah and his messenger Rose who later shows up at the Salvatore Boarding house.
Stefan calls Elena over and Rose tells them about another, even more feared, Original called Klaus. Of course, the siblings mostly think it's a legend. Roxie leaves for Europe to try and find out more about the Original vampires.
She comes back in Daddy Issues, walking into the Grill only to follow Damon who says he has "important vampire rescuing business". The three Salvatores get surrounded by Jules' werewolf pack. They fight them while Tyler saves Caroline but are about to lose when Elijah's witch save them to keep the Original vampire's promise to Elena. Later, Roxie comes home to Damon with John Gilbert and reveals that she's been with him for a short while before coming back and that he has something for them; a dagger that can kill an Original vampire that Isobel is planning to use to neutralize Klaus.
In Crying Wolf Roxie comes home to the Boarding House after an evening at the Grill but notices quickly that something is wrong. After investigating and finding out the wolves left in Jules pack are torturing Damon she goes to get Elijah who once again saves Damon's life by killing the rest of the werewolves except Jules.In The Dinner Party the murder of Elijah is planned but there are few bumps in the road on their way to get there. Roxie attends the dinner and doesn't even seem surprised by how her brothers can't seem to get their facts straight before deciding to do something really stupid. In the end however they do manage to neutralize Elijah and locks him up in the basement of the Boarding House with the dagger still in his chest. Their happiness isn't long lasting though, since Elijah's compulsion wares off on Katherine after his death and she gets out of the tomb. She's staying at the Salvatore Boarding house and the siblings are having a hard time dealing with her presence. However, Katherine turns out to be of help when Elena is in danger but that doesn't exactly change their opinion on her.
- Damon: "This is Isobel's stuff. It's definitely the right place."
- Stefan: "Where are they?"
- Damon: "I don't know, Stefan."
- Roxie: "At a better hiding place. Just a guess."
- — The Salvatores at Isobel's house.
Roxie attends the 60's decade dance with Damon despite the two not being in High School. She shows to be irritated when the fun is interrupted by Klaus who apparently has possessed Alaric's body but they know they have to stop him. Damon, Roxie and Bonnie come up with a plan in secret in which Bonnie dies. Elena is upset and angry but Damon explains their plan while Roxie takes Jeremy and Bonnie to the Witch Burial Ground where Bonnie wakes up again and Roxie goes back to the Boarding House.
During the night Elena undaggers Elijah but he doesn't wake up until the next day. She leaves with him and Stefan is worried because he can't find her when he wakes up. They soon realize both Elijah and Elena are gone but as much as Roxie is afraid of Elijah will come back to hurt her or her brothers she takes Stefan's side and trusts that Elena for once knows what she's doing.
In The Last Day it's the night of the full moon and Klaus prepares the sacrifice to break the hybrid curse placed on him. In the meantime, Damon isn't prepared to rely on Elijah's elixir to save Elena's life so he feeds her his blood. Stefan stops him and they fight ending with Stefan getting stabbed by Damon. Roxie is furious and yells at Damon all the way back to the parlor with her last words being "I'm done. You're on your own". Then she leaves Mystic Falls.
She comes back in the season finale after she gets a message from Stefan saying Damon's been bitten by Tyler Lockwood. Roxie feels bad about arguing with him and says sorry for everything while he's locked in the basement. When Alaric comes to pay Damon a visit Roxie goes upstairs but is knocked out with vervain by the Sheriff. However, Caroline convinces her mother to release Roxie.