Ikpeazu, 26, will add a much-needed central striking option for Boro following the exits of Britt Assombalonga and Ashley Fletcher, with his arrival following on from the acquisition of winger Sammy Ameobi.
The one-time Hearts forward, who spent a loan spell at Doncaster Rovers early in his career, scored against Boro at Adams Park at the start of January and was the Chairboys' top-scorer last term.
He has joined for an initial £750,000 fee, which will rise to £1m with add-ons.
Boro boss Neil Warnock said: “I’ve always liked Uche back to when he was at Hearts and I watched him a few times. He looks raw at times but he’s so keen and dedicated wherever he plays and I think the fans will really get behind him because he’s such a 100% player.
“I was really impressed in my meetings with him with his dedication and desire to do well for Middlesbrough. I’m really looking forward to working with him.”