Who was President during the first flight of the space shuttle?
President Ronald Reagan.
Depending on what you consider the first flight, the answer is either Ronald Reagan (President January 20, 1981 - January 20, 1989) or Jimmy Carter (President January 20, 1977 - January 20, 1981).
First flight; Attached to Enterprise Shuttle Carrier Aircraft throughout flight.
First free flight; Tailcone on; lakebed landing
Third free flight; First with no tailcone; lakebed landing
Final Enterprise free flight; First landing on Edwards AFB concrete runway.
First Columbia flight, first orbital test flight; STS-1
Enterprise never flew in space but it did fly in the atmosphere. If you consider Enterprise to count as one of the space shuttles, then the first flight was in 1977 under Carter. If you only count the flights that launched into space, then Columbia was the first flight and occurred in 1981 under Reagan.