Avtandil Makharadze started his acting career as a student at Shota Rustaveli Theatre and Film University with performances in the acts of his fellow students.
His role in the play "The Merchant of Venice", where he played Shylock caught the eyes of critics and the public.
He worked at Shota Rustaveli Theatre until 1991 where he had played over 50 roles.
He had great success in the theater of MHAT (Moscow Art Theatre), where in 1983, he played the main role in the play "Collapse" (Jaqo's Dispossessed). The same role was previously played in a television series under the same title on Georgian Television, which was one of the most controversial TV Plays of Soviet Georgia.
In 1984 Avtandil Makharadze played two main parts in the famous film by Tengiz Abuladze "Repentance", (those of Varlam and Abel Aravidze).
In 1987 at the Cannes Film Festival "Repentance" won the Grand Prize of the Jury, Prize of the Ecumenical Jury and the FIPRESCI Award. The same year, at the Chicago Film Festival Avtandil Makharadze received Silver Hugo Award for the best male performance. He won the first ever NIKA award at the Moscow international Film Festival in 1987 as well.
In 1989 he starred alongside Isabelle Huppert, Bernard Blier, Erland Josephson, Richard Berry and Miki Manojlovic in Aleksandar Petrovic's last film "Seobe".
In 1991, Avtandil Makharadze played the main role in the film of Georgian director Mikheil Kalatozishvili "The Chosen One". The Film was nominated for Golden Bear at the Berlin International Film Festival.
In 1993 he received Golden Eagle at The Tbilisi International Film Festival for the best male performance in Vagif Mustafayev film "Out of".
In 2004 Avtandil Makharadze starred in Vagif Mustafayev's film "National Bomb" which was nominated for Golden St. George at the Moscow International Film Festival. Avtandil Makharadze won the best male performance award at the Smolensk Film Festival for that part.