The fabrication and performance of a microfluidic device with integrated liquid-core optical waveguides for laser induced fluorescence DNA fragment analysis is presented. The device was fabricated through poly(dimethylsiloxane) (PDMS) soft lithography and waveguides are formed in dedicated channels through the addition of a liquid PDMS pre-polymer of higher refractive index. Once a master has been fabricated, microfluidic chips can be produced in less than 3 h without the requirement for a cleanroom, yet this method provides an optical system that has higher performance than a conventional confocal optical assembly. Optical coupling was achieved through the insertion of optical fibers into fiber-to-waveguide couplers at the edge of the chip and the liquid–fiber interface results in low reflection and scattering losses. Waveguide propagation losses are measured to be 1.8 dB cm⁻¹ (532 nm) and 1.0 dB cm⁻¹ (633 nm). The chip displays an average total coupling loss of 7.6 dB due to losses at the optical fiber interfaces. In the electrophoretic separation and detection of a BK virus PCR product, the waveguide system achieves an average signal-to-noise ratio of 570 ± 30 whereas a commercial confocal benchtop electrophoresis system achieves an average SNR of 330 ± 30. To our knowledge, this is the first time that a waveguide-based system has been demonstrated to have a SNR comparable to a commercially available confocal-based system for microchip capillary electrophoresis.