The 31-year-old goalkeeper has signed a two-year deal at the Riverside Stadium and follows fellow new recruit Victor Valdes to the newly-promoted Premier League club.
The United States of America international made 144 appearances during eight top-flight seasons with Aston Villa, which came to an end in May.
Guzan, who has over 50 caps for his country, featured in 28 Premier League matches last term as Villa finished 20th.
As well as Valdes, Guzan joins fellow new recruits Marten De Roon, Antonio Barragan and Alvaro Negredo on Teesside ahead of the new Premier League season.
Boro beat Saudi Arabian champions Al-Ahli 2-0 in their latest pre-season match. Their next test comes at Guzan's old club Aston Villa on Saturday.
Middlesbrough’s first league match of 2016/17 is a home meeting with Stoke City on Saturday 13 August.
For 10 facts about Middlesbrough's latest signing, and more on Guzan's transfer, visit mfc.co.uk.