The "Finding Dory" star, who hosts her own top-rated daytime talk show in America, picked up her 20th, 21st and 22nd awards at the Microsoft Theater.
Singer-actor Justin Timberlake presented her with the favourite daytime TV host and favourite animated movie voice trophies, while her sketch romp around a shopping mall with Britney Spears, which aired on her show last year, earned her the favourite comedic collaboration prize.
Handing her another three honours, Timberlake called Ellen "one of my very good friends" and "one of the best people on this planet".
"This is amazing. 20 is ... 17, I get it, 18, sure, 19, I can see it. But 20, this is outrageous. This is really something that means more to me because it comes from the people," DeGeneres said while accepting the honour.
"And everybody keeps thanking the people and it's redundant but you are the people who are responsible for me being up there so I say thank you people."
DeGeneres' "Finding Dory" film was also named favourite movie and favourite family movie at the ceremony.
Timberlake was also a big winner at the awards bash, picking up favourite male artist and favourite song for "Can't Stop The Feeling."
Blake Shelton was another double winner, making history as the first country act ever to win a People's Choice favourite album award and landing the favourite male country artist prize.
It was also a huge night for girl group Fifth Harmony, who performed for the first time as a four-piece.
The quartet wowed the audience and viewers at home by wearing revealing black leather outfits for a raunchy rendition of their "Work From Home" hit.
The band, who also picked up the favourite group prize for a second successive year, were stunned by the departure of Camila Cabello last month.
Johnny Depp put his tough year behind him to win the award for favourite movie icon while Robert Downey Jr took home the favourite action movie actor gong.
Tyler Perry picked up the award for favourite humanitarian at the event, which was hosted by Joel McHale.