Interstate 280 is the designation for several Interstate Highways in the United States, all of which are related to Interstate 80:

• Interstate 280 (California), a north-south freeway running from San Jose, California to San Francisco, California.
• Interstate 280 (Illinois-Iowa), part of the beltway around the Quad Cities of Illinois and Iowa.
• Interstate 280 (New Jersey), a connector in Newark, New Jersey from Interstate 80 to Interstate 95.
• Interstate 280 (Ohio), a connector in Toledo, Ohio from Interstate 80 to Interstate 90.

The following roads used to be numbered I-280:

• Interstate 276, when I-76 was I-80S .
• Interstate 680 (Nebraska-Iowa)