This center was one of the first modern retail project developed in the Portland area for years. The Target store at the Maine Crossing was the first in the state of Maine when it opened in October 2001. Mens Warehouse and Famous footwear opened in December 2001. In 2002, GameStop, Sprint and Starbucks Coffee opened in a free-standing building in the parking lot. A.C.Moore opened in 2002 too in the main store block of the complex.  This block contains Famous Footwear, Old Navy, Babies ‘r’ us and Mattress Giant.

The Maine Crossing is highly visible from I-95 and near the Maine Mall. The developer of this center proposed a similar project in Greenland, NH near Portsmouth. This new shopping center also features a Target store. In 2012, Old Navy has closed and moved.

In 2013, Nordstrom Rack opened in the 30,000 sq.ft. space left vacant by Old Navy. In January 2018, Toys r us announced the closing of 180 U.S. stores including the South Portland Babies 'r' us location. In November 2019, A.C.Moore announced the closing of all of its stores. 

In 2021, Burlington Stores announced it would relocate its existing South Portland location neat the airport to the Maine Crossing. The store will be located between Nordstom Rack and Men's Wearhouse. In April 2023, Bed Bath & Beyond filed for bankruptcy and confirmed it would close all remaining stores, so the South Portland store has closed in 2023.  Barnes & Noble opened a new store in the former Bed Bath & Beyond in May 2024.