The final flight is scheduled for an 11 a.m. departure from San Fransisco and a 2:45 p.m. arrival in Honolulu.
Aboard the flight, there will be a celebration of United's very first 747 flight in 1970 with the same route and 1970s-inspired menu, entertainment and crew uniforms.
The retro feel "will help send the Queen of the Skies off in true style," United said in a statement.
The 747 has generally been used for international flights. The last United Airlines international flight for the 747 was on October 29, from Seoul, South Korea, to San Francisco.
Once United's farewell 747 flight touches down in Honolulu today, Delta will be the only U.S. carrier flying passengers in the jet. Delta's final 747 flight is scheduled for later this year.
The flight can be followed with the #UA747Farewell hashtag on social media posts or on a trackingwebsite and searching with the aircraft's tail number N118UA or flight number UA747.