Padilla parents divorced when he was two-years-old, which he has said did not greatly affect him. According to his video "Draw My Life," he has two younger brothers.
By his own account, Padilla has said that he was very introverted as a child, due in part to anxiety issues that would affect him when he received attention from others. He has also spoken about having aspirations to get into game design when he was a child.
Padilla suffers from anxiety, in which he experiences panic attacks often. He has said that due to his mother having a similar issue, he believes this condition to be hereditary in his family.
Padilla began his YouTube career in 2005, posting to the Smosh channel with long-time YouTube co-creator and friend Ian Hecox. The duo originally posted lip-sync videos, a common video type at the time which featured the stars lip-sync singing a particular song whilst performing entertaining or comedic gestures. The earliest of their lip-sync videos, "Mortal Kombat Theme" and "Pokemon Theme" gained significant notoriety, both appearing on YouTube Front Page (a now-defunct feature similar in functionality to YouTube Spotlight).
The success of their lip-sync videos garnered a significant following for Padilla and Hecox, inspiring them to write and produce more detailed comedic videos, which primarily involved various skits. The skits they created as early as 2006 set the stage for their continued success on YouTube.
In addition to the Smosh channel and all associated channels, Padilla concurrently operated his own self-named channel from 2006 to 2013. The channel has amassed over 1 million subscribers, as of August 8, 2013, but has suffered consistency issues since its launch. In 2013, the AnthonyPadilla channel took an indefinite hiatus. Padilla himself has not commented as to whether or not the channel will continue.
Anthony's final video on his personal channel mentions he will be doing daily videos on his snapchat. His snapchat name is anth0nypadilla.
Padilla has had multiple relationships during his YouTube stardom, but many of them have been predominantly private and rather unknown.
Padilla began dating fellow YouTuber Kalel Cullen in 2010. The couple became engaged in 2013, when they launched their WatchUsLiveAndStuff channel; a daily account of their life. In December 2014, Padilla and Cullen announced via YouTube that they had decided to split, citing irreconcilable differences. However, in his recently uploaded Draw My Life video, he says that Kalel manipulated and used him, although he did not specifically say her name at all in the video. He also goes into greater detail about his anxiety and panic attacks, life as a child with divorced parents, and how he started Smosh along with Ian.
Since his breakup with Cullen, Padilla has not continued video blogging, thus mostly disconnecting his personal life from his fan-base. However, he has recently become active on his personal channel alongside Miel.
Anthony is currently dating Miel Bredouw, a former popular viner under the name mielmonster, though not publicly announced by either of them. Miel owns a vegan bakery in LA and is also a singer. Anthony and Miel have traveled to Iceland, Boston, Vermont, Mexico, and various other places together.
Padilla has a self-named channel, on which he would post video blogs. The channel has over 1 million subscribers and was inactive since March 2013. However, he has recently started to post a few videos in 2016 featuring Miel and their adventures together.