In this paper we describe a new process for fabricating ultra-thick microfluidic devices utilizing SU-8 50 negative photoresist (PR) by standard UV lithography. Instead of using a conventional spin coater, a simple 'constant-volume-injection' method is used to create a thick SU-8 PR film up to 1.5 mm with a single coating. The SU-8 PR is self-planarized during the modified soft-baking process and forms a highly-uniform surface without any edge bead effect, which commonly occurs while using a spin coater. Photomasks can be in close contact with the PR and a better lithographic image can be generated. Experimental data show that the average thickness is 494.32 ± 17.13 μm for a 500 μm thick film (n = 7) and the uniformity is less than 3.1% over a 10 × 10 cm2 area. In this study, the temperatures for the soft-baking process and post-exposure baking are 120 °C and 60 °C, respectively. These proved to be capable of reducing the processing time and of obtaining a better pattern definition of the SU-8 structures. We also report on an innovative photomask design for fabricating ultra-deep trenches, which prevents the structures from cracking and distorting during developing and hard-baking processes. In this paper, two microfluidic structures have been demonstrated using the developed novel methods, including a micronozzle for thruster applications and a microfluidic device with micropost arrays for bioanalytical applications.