The impact of fermentation (Saccharomyces cerevisiae ATCC 9763) on the bioaccessibility of lycopene in a model tomato juice was examined. The physicochemical and structural properties of the tomato tissue were determined after fermentation and the bioaccessibility of lycopene was monitored using a simulated gastrointestinal tract. A lycopene concentration of 45.1 mg/100 g was obtained under optimal fermentation conditions. The cell walls of the tomato cells were hydrolyzed and disrupted by fermentation. Cell disruption decreased the pectin content and reduced the tissue fragment size, thereby reducing gravitational separation and facilitating lycopene release. The lycopene bioaccessibility in the tomato juices increased in the following order: unfermented (8.5%) < fermented (11.4%) < unfermented-emulsified (13.6%) < fermented-emulsified (22.7%). These effects were attributed to a combination of greater tomato tissue disruption and enhanced mixed micelle formation. Our results may be useful for the development of functional foods and beverages with improved health benefits.