The use of a seven-way clostridial vaccination is the most common, cheapest, and efficacious preventative measure taken against blackleg. Burning the upper layer of soil to eradicate left-over spores is the best way to stop the spread of blackleg from diseased cattle. Diseased cattle should be isolated. Treatment is generally unrewarding due to the rapid progression of the disease, but penicillin is the drug of choice for treatment. Treatment is only effective in the early stages and as a control measure.

Dr. Oliver Morris (O.M.) Franklin made a significant contribution to the welfare of cattle and the livestock industry with his development of the blackleg vaccine. Franklin developed the original method of giving the vaccine while at Kansas State Agriculture College using live cattle. Franklin and another graduate veterinarian founded the original Kansas Blackleg Serum Co. in Wichita in 1916.

When infection begins, the animal may develop a fever, and the affected limb can feel hot to the touch. The limb usually swells significantly, and the animal can develop lameness on the affected leg. Crepitation (the sensation of air under the skin) can be noticed in many infections, as the area seems to crackle under pressure.

Once clinical signs develop, the animal may only live a short while, sometimes as few as 12 hours. Occasionally, cattle succumb to the disease without showing any symptoms, and only a necropsy reveals the cause. During a necropsy, a diagnosis is usually made very quickly, as the affected muscle is usually mottled with black patches, which are dead tissue, killed by the toxins the bacteria release when they infect live tissue. If viewed under a microscope, small rod-like bacteria can be seen to confirm the diagnosis.

The bacteria can survive in the rhizosphere of other crops such as tomato, carrots, sweet potato, radish, and squash as well as weed plants like lupin and pigweed, so it is very hard to get rid of it completely. When it is known that the bacterium is present in the soil, planting resistant varieties can be the best defense against the disease. Many available beet cultivars are resistant to "Pectobacterium carotovorum" subsp. "betavasculorum", and some examples are provided in the corresponding table. A comprehensive list is maintained by the USDA on the Germplasm Resources Information Network.

Even though some genes associated with root defense response have been identified, the specific mechanism of resistance is unknown, and it is currently being researched.

Some bacteriophages, viruses that infect bacteria, have been used as effective controls of bacterial diseases in laboratory experiments. This relatively new technology is a promising control method that is currently being researched. Bacteriophages are extremely host-specific, which makes them environmentally sound as they will not destroy other, beneficial soil microorganisms. Some bacteriophages identified as effective controls of "Pectobacterium carotovorum" subsp. "betavasculorum" are the strains ΦEcc2 ΦEcc3 ΦEcc9 ΦEcc14. When mixed with a fertilizer and applied to inoculated calla lily bulbs in a greenhouse, they reduced diseased tissue by 40 to 70%. ΦEcc3 appeared to be the most effective, reducing the percent of diseased plants from 30 to 5% in one trial, to 50 to 15% in a second trial. They have also been used successfully to reduce rotting in lettuce caused by "Pectobacterium carotovorum" subsp. "carotovorum", a different bacterial species closely related to the one that causes beet vascular necrosis.

While it is more difficult to apply bacteriophages in a field setting, it is not impossible, and laboratory and greenhouse trials are showing bacteriophages to potentially be a very effective control mechanism. However, there are a few obstacles to surmount before field trials can begin. A large problem is that they are damaged by UV light, so applying the phage mixture during the evening will help promote its viability. Also, providing the phages with susceptible non-pathogenic bacteria to replicate with can ensure there is adequate persistence until the bacteriophages can spread to the targeted bacteria. The bacteriophages are unable to kill all the bacteria, because they need a dense population of bacteria in order to effectively infect and spread, so while the phages were able to decrease the number of diseased plants by up to 35%, around 2,000 Colony Forming Units per milliliter (an estimate of living bacteria cells) were able to survive the treatment. Lastly, the use of these bacteriophages places strong selection on the host bacteria, which causes a high probability of developing resistance to the attacking bacteriophage. Thus it is recommended that multiple strains of the bacteriophage be used in each application so the bacteria do not have a chance to develop resistance to any one strain.