Envoy Air's AA3599 flew from Miami to Caracas on Thursday, carrying US energy official Jarrod Agen; American plans a second daily flight from 21 May.
The restart follows Washington's reopening of its embassy in Caracas and restored diplomatic ties, months after US forces captured then-president Nicolas Maduro in a January raid.
Direct flights had been suspended since 2019 over US security concerns, forcing travellers onto indirect regional routes; officials and passengers said the service would reconnect families and support business.
Beyond restored flights, is Venezuela truly safe for families to reunite after years of turmoil?
Will economic recovery in Venezuela, backed by the U.S., lead to genuine democratic reform?
How will Venezuela's new government protect foreign investments from its history of asset seizure?