We demonstrate a hybrid “package-less” polydimethylsiloxane (PDMS)–complementary metal–oxide–semiconductor (CMOS)-FR4 system for contact imaging. The system embeds the CMOS image sensor directly in a PDMS layer instead of the standard chip package to support microfluidic structures much larger and more complex than those in prior art. The CMOS/PDMS layer is self-aligned to form a continuous, flat surface to provide structural support for upper microfluidic layers. The system consists of five layers of PDMS implementing fluid channels, valves, chambers, and inlets/outlets. A custom CMOS image sensor with integrated signal conditioning circuits directly captures light from sample fluid for high optical collection efficiency. Owing to the flexibility afforded by the integration process, the system demonstrates, for the first time, integrated valves in contact imaging. Moreover, we present the first direct comparison of the optical performance of a CMOS image sensor and a photomultiplier tube (PMT) in identical contact-imaging conditions. Measurements show that our CMOS sensor achieves 17 dB better signal-to-noise ratio (SNR) compared with a commercial PMT across a broad range of integration times, with a maximum SNR of 47 dB. Chemiluminescent testing successfully shows signal detection for different analyte concentrations and integration times. The contact-imaging system demonstrates a detection limit of 25 μM of a 9,10-diphenylanthracene-based solution.