Supreme Leader Ayatollah Ali Khamenei, Iran's most powerful figure, is a hardliner. This is in contrast to centrist President Hassan Rouhani, architect of its nuclear deal with six international powers last year.
Speaking during a live broadcast on state TV, Khamenei said: "America has continued its enmity toward Iran since (the 1979 Islamic) revolution ... It is a huge mistake to trust evil Britain and the great satan (the US)."
"We will not cooperate with America over the regional crisis. Their aims in the region are 180 degrees opposed to Iran's."
He also questioned the US' commitment to last year's nuclear deal. The economic sanctions on Iran have been lifted, but some US sanctions remain and US banks can't do business with Iran directly or indirectly.
"They use human rights, terrorism ... as pretexts to avoid fulfilling their commitments," Khamenei said.
"If we remain strong and united and revolutionary, those who are trying to bully Iran and are against us will not succeed."
He made the comments at a gathering to commemorate the anniversary of the death of the revolution's founder, Ayatollah Rouhollah Khomeini, in 1989.